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Transcriptional (dys)regulation and aging in Caenorhabditis
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Guest







PostPosted: Mon Oct 27, 2008 9:56 pm    Post subject: Transcriptional (dys)regulation and aging in Caenorhabditis Reply with quote

This may interest those familiar with the recent Kim et al article
reviewed in Scientific American. Moreover that there is a
developmental drift. I>ve been interested in something like this for a
while. Skulahev is looking for a rather dubious longevity clock,
however evolution only caares about keeping you alive long enough to
reprodice.



Genome Biol. 2008 Sep 16;9(9):233. [Epub ahead of print] Links
Transcriptional (dys)regulation and aging in Caenorhabditis
elegans.Pincus Z, Slack FJ.
Department of Molecular, Cellular and Developmental Biology, Yale
University, New Haven, CT 06520, USA. frank.slack@yale.edu.

ABSTRACT: A circuit of transcription factors has been discovered in
Caenorhabditis elegans that could provide a link between laboratory-
defined intracellular 'longevity pathways', gene dysregulation and the
process of normal aging.

PMID: 18828877 [PubMed - as supplied by publisher]
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Lou Pagnucco
Guest






PostPosted: Tue Oct 28, 2008 7:11 pm    Post subject: Re: Transcriptional (dys)regulation and aging in Caenorhabdi Reply with quote

On Oct 27, 5:56 pm, timoth...@my-deja.com wrote:
[quote]This may interest those familiar with the recent Kim et al article
reviewed in Scientific American. Moreover that there is a
developmental drift. I>ve been interested in something like this for a
while. Skulahev is looking for a rather dubious longevity clock,
however evolution only caares about keeping you alive long enough to
reprodice.

Genome Biol. 2008 Sep 16;9(9):233. [Epub ahead of print] Links
Transcriptional (dys)regulation and aging in Caenorhabditis
elegans.Pincus Z, Slack FJ.
Department of Molecular, Cellular and Developmental Biology, Yale
University, New Haven, CT 06520, USA. frank.sl...@yale.edu.

ABSTRACT: A circuit of transcription factors has been discovered in
Caenorhabditis elegans that could provide a link between laboratory-
defined intracellular 'longevity pathways', gene dysregulation and the
process of normal aging.

PMID: 18828877 [PubMed - as supplied by publisher]
[/quote]
Thanks for posting this.

Without access to the paper, I assume that it focuses on the authors'
premise that microRNAs play a critical role in orchestrating
development,
differentiation and aging.

Here is one of the earlier abstracts:
'A Developmental Timing MicroRNA and Its Target Regulate Life Span in
C. elegans'
Michelle Boehm and Frank Slack
The microRNA lin-4 and its target, the putative transcription factor
lin-14, control the timing of larval development in Caenorhabditis
elegans. Here, we report that lin-4 and lin-14 also regulate life
span
in the adult. Reducing the activity of lin-4 shortened life span and
accelerated tissue aging, whereas overexpressing lin-4 or reducing
the activity of lin-14 extended life span. Lifespan extension
conferred
by a reduction in lin-14 was dependent on the DAF-16 and HSF-1
transcription factors, suggesting that the lin-4–lin-14 pair affects
life span through the insulin/insulin-like growth factor–1 pathway.
This work reveals a role for microRNAs and developmental timing
genes in life-span regulation.

The complete paper is available at:
http://www.sciencemag.org/cgi/content/full/310/5756/1954
or as PDF at:
http://www.sciencemag.org/cgi/reprint/310/5756/1954.pdf

Here is a patent for RNA interference to nullify the MicroRNAs
Hn-14, Iin-28, lin-42, egl-35 (Did Kim>s paper look at egl-35?)
(WO/2007/002528) ANTI-AGING MICRORNAS
It is issued to the above authors Boehm, Slack and Yalue U.
http://www.wipo.int/pctdb/en/wo.jsp?WO=2007002528

A few related links:

MicroRNA, Cell Fate Maintenance, and Aging
http://www.santafe.edu/events/workshops/index.php/MicroRNA%2C_Cell_Fate_Maintenance%2C_and_Aging

MicroRNA Gene that Regulates Lifespan Found by Yale Scientists
http://www.emaxhealth.com/8/4120.html

"The Temporal Patterning MicroRNA let-7 Regulates Several
Transcription Factors at the Larval to Adult Transition in C.
elegans".
http://www.euchromatin.com/Grosshans01.htm

MicroRNA, the putative molecular control for mid-life decline
- Eugenia Wang
doi:10.1016/j.arr.2007.02.004

Wang is the scientist who discovered years ago that some
small (then unknown) factor in blood serum from old donors
suppressed muscle cell growth in vitro. I surmise that the factor(s)
were microRNAs or their interfering complements.
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Lou Pagnucco
Guest






PostPosted: Tue Oct 28, 2008 11:12 pm    Post subject: Re: Transcriptional (dys)regulation and aging in Caenorhabdi Reply with quote

On Oct 28, 3:11 pm, Lou Pagnucco <pagnu...@htdconnect.com> wrote:
[quote]On Oct 27, 5:56 pm, timoth...@my-deja.com wrote:





This may interest those familiar with the recent Kim et al article
reviewed in Scientific American. Moreover that there is a
developmental drift. I>ve been interested in something like this for a
while. Skulahev is looking for a rather dubious longevity clock,
however evolution only caares about keeping you alive long enough to
reprodice.

Genome Biol. 2008 Sep 16;9(9):233. [Epub ahead of print] Links
Transcriptional (dys)regulation and aging in Caenorhabditis
elegans.Pincus Z, Slack FJ.
Department of Molecular, Cellular and Developmental Biology, Yale
University, New Haven, CT 06520, USA. frank.sl...@yale.edu.

ABSTRACT: A circuit of transcription factors has been discovered in
Caenorhabditis elegans that could provide a link between laboratory-
defined intracellular 'longevity pathways', gene dysregulation and the
process of normal aging.

PMID: 18828877 [PubMed - as supplied by publisher]

Thanks for posting this.

Without access to the paper, I assume that it focuses on the authors'
premise that microRNAs play a critical role in orchestrating
development,
differentiation and aging.

Here is one of the earlier abstracts:
'A Developmental Timing MicroRNA and Its Target Regulate Life Span in
C. elegans'
Michelle Boehm and Frank Slack
The microRNA lin-4 and its target, the putative transcription factor
lin-14, control the timing of larval development in Caenorhabditis
elegans. Here, we report that lin-4 and lin-14 also regulate life
span
in the adult. Reducing the activity of lin-4 shortened life span and
accelerated tissue aging, whereas overexpressing lin-4 or reducing
the activity of lin-14 extended life span. Lifespan extension
conferred
by a reduction in lin-14 was dependent on the DAF-16 and HSF-1
transcription factors, suggesting that the lin-4–lin-14 pair affects
life span through the insulin/insulin-like growth factor–1 pathway.
This work reveals a role for microRNAs and developmental timing
genes in life-span regulation.

The complete paper is available at:http://www.sciencemag.org/cgi/content/full/310/5756/1954
or as PDF at:http://www.sciencemag.org/cgi/reprint/310/5756/1954.pdf

Here is a patent for RNA interference to nullify the MicroRNAs
Hn-14, Iin-28, lin-42, egl-35 (Did Kim>s paper look at egl-35?)
(WO/2007/002528) ANTI-AGING MICRORNAS
It is issued to the above authors Boehm, Slack and Yalue U.http://www.wipo.int/pctdb/en/wo.jsp?WO=2007002528

A few related links:

MicroRNA, Cell Fate Maintenance, and Aginghttp://www.santafe.edu/events/workshops/index.php/MicroRNA%2C_Cell_Fa...

MicroRNA Gene that Regulates Lifespan Found by Yale Scientistshttp://www.emaxhealth.com/8/4120.html

"The Temporal Patterning MicroRNA let-7 Regulates Several
Transcription Factors at the Larval to Adult Transition in C.
elegans".http://www.euchromatin.com/Grosshans01.htm

MicroRNA, the putative molecular control for mid-life decline
- Eugenia Wang
doi:10.1016/j.arr.2007.02.004

Wang is the scientist who discovered years ago that some
small (then unknown) factor in blood serum from old donors
suppressed muscle cell growth in vitro.  I surmise that the factor(s)
were microRNAs or their interfering complements.- Hide quoted text -

- Show quoted text -
[/quote]
Another paper that might be of interest:

"MicroRNAs: Relevance to Aging and Age-Related Diseases"
Open Longevity Science, 2008, 2, 66-75
Available at URL (scroll down to pp. 66-75):
http://www.bentham.org/open/tolsj/openaccess-2.htm
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Guest







PostPosted: Wed Oct 29, 2008 8:51 pm    Post subject: Re: Transcriptional (dys)regulation and aging in Caenorhabdi Reply with quote

I haven>t seen the complete Kim et al paper in CELL. Here>s an
abstract I posted a while back. In rats there is about a 40% decrease
in methylation over the lifespan.


Aging Cell. 2006 Jun;5(3):235-46. Related Articles, Links

Modulated microRNA expression during adult lifespan in Caenorhabditis
elegans.


Ibanez-Ventoso C, Yang M, Guo S, Robins H, Padgett RW, Driscoll M.


Department of Molecular Biology and Biochemistry, Rutgers, The State
University of New Jersey, Nelson Biological Laboratories, 604 Allison
Road, Piscataway NJ 08854, USA.


MicroRNAs (miRNAs) are small, abundant transcripts that can bind
partially homologous target messages to inhibit their translation in
animal cells. miRNAs have been shown to affect a broad spectrum of
biological activities, including developmental fate determination,
cell
signaling and oncogenesis. Little is known, however, of miRNA
contributions to aging. We examined the expression of 114 identified
Caenorhabditis elegans miRNAs during the adult lifespan and find that
34 miRNAs exhibit changes in expression during adulthood (P</= 0.05),
31 with more than a twofold level change. The majority of age-
regulated
miRNAs decline in relative abundance as animals grow older.
Expression
profiles of developmental timing regulators lin-4 and let-7 miRNAs,
as
well as conserved muscle miRNA miR-1, show regulation during
adulthood.
We also used bioinformatic approaches to predict miRNA targets
encoded
in the C. elegans genome and we highlight candidate miRNA-regulated
genes among C. elegans genes previously shown to affect longevity,
genes encoding insulin-like ligands, and genes preferentially
expressed
in C. elegans muscle. Our observations identify miRNAs as potential
modulators of age-related decline and suggest a general reduction of
message-specific translational inhibition during aging, a previously
undescribed feature of C. elegans aging. Since many C. elegans
age-regulated miRNAs are conserved across species, our observations
identify candidate age-regulating miRNAs in both nematodes and
humans.


PMID: 16842496 [PubMed - in process]
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Guest







PostPosted: Wed Oct 29, 2008 9:24 pm    Post subject: Re: Transcriptional (dys)regulation and aging in Caenorhabdi Reply with quote

The article in CELL found that the ELT transcription factors were
homologous with GATA tracscription factors in mammals.
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